Overall High throughput data production technologies, particularly next generation DNA sequencing, have ushered in the most disruptive changes to biomedical research in decades. Making sense of the large datasets produced by high throughput technologies requires sophisticated statistical and computational methods, as well as substantial computational power. This has led to an acute crisis in biomedical research, as researchers without informatics training attempt to perform computation-dependent analyses. Since 2005, the Galaxy project has been working to address this problem by providing a framework that makes advanced computational tools usable by non-experts. Galaxy seeks to make data-intensive research more accessible, transparent, and reproducible by providing a Web-based environment in which users can perform computational analyses and have all of the details automatically tracked for later inspection, publication, or reuse. In the proposed project, we will improve Galaxy in several specific ways. We will greatly increase Galaxy's usability for working with large numbers of datasets. Modern experiments often involve hundreds of datasets organized in complex ways; we will make analyzing such data simple and intuitive. We will improve the development and distribution of software tools, making it much easier for developers to distribute tools and for users to acquire them, all while preserving provenance. We will greatly improve access to a wide variety of computational resources such as cloud computing and high- performance clusters, enabling biomedical researchers to use resources that have traditionally been difficult to work with. Finally, we will engage in training, outreach, and dissemination, including the development of scalable training materials that can be used by others to conduct biomedical data analysis training.